The isolation and characterization of defined populations of immunologically competent human T, B and Null cells and their products should facilitate investigations directed at an understanding of the cellular mechanisms involved in the generation of the immune response. The intention here is to take advantage of major recent developments of in vitro methods for the characterization and identification of human lymphocyte classes by cell surface markers, of new techniques for the isolation of purified subsets of lymphocytes and monocytes and of in vitro methods permitting the functional analysis and interactions of these isolated subsets of cells. We plan to isolate and purify subsets of human T cells at high yields with the view of ascertaining whether individually or in reconstituted pools, they mediate a wide variety of immunologic activities in vitro, including the response to antigen, mitogens, cytotoxic functions, mediator production, regulatory functions, such as T-T, T-B and T-Null interactions, and the genetic controls of such interactions. These studies will be facilitated by identification of alloantisera from patients with autoimmune disease and by the development of heteroantisera utilizing absorption techniques, by hybridization studies and by isolation of T cell membrane antigens to define the heterogeneity which exists within the human T cell pool in terms of helper, suppressor and amplifer cells, and specific effector cells. These reagents should permit us to examine the differentiative history of the human T cell and develop an understanding of the regulatory events necessary for the differentiation of specific effector populations in man.